There today exist a number of automated donor hemapheresis systems for the separation of blood, including whole blood, into components or fractions. The systems are designed: to collect one or more components, such as plasma, white cells, platelets and red cells, for further use or for disposal; to return certain components to the donor, who may be a patient; and/or to treat a component, for subsequent return to a donor. One such system is the Autopheresis-C.RTM. system sold by Baxter Healthcare Corporation of Deerfield, Ill., a wholly owned subsidiary of the assignee of the present invention. That system utilizes a microprocessor-controlled instrument including automated processing programs, in conjunction with a disposable set. The Autopheresis-C.RTM. device may, when a disposable plasmapheresis set is installed therein, be used to collect plasma from whole blood drawn from a donor. A rotating membrane in a separation chamber of the disposable may in fact be wetted by an anticoagulant priming operation before blood is withdrawn from the donor, as shown in U.S. patent application Ser. No. 07/106,089, filed Oct. 7, 1987, entitled "Method for Wetting a Plasmapheresis Filter with Anticoagulant", and corresponding PCT International Application Publication No. W089/03229.
For the collection of platelets and plasma, the Autopheresis-C.RTM. system uses a single, two stage set as disclosed in U.S. Pat. No. 4,851,126, entitled "Apparatus and Methods for Generating Platelet Concentrate". The set may include a rotating membrane separation chamber as set forth in U.S. patent application Ser. No. 73,378 and in corresponding Canadian Patent No. 1,261,765, as well as a centrifuge separator as set forth in U.S. Pat. Nos. 4,776,964 and 4,911,833 entitled "Closed Hemapheresis System and Method" and in International PCT Publication No. W088/05332 entitled "Continuous Centrifugation System and Method for Directly Deriving Intermediate Density Material from a Suspension". If an anticoagulant source is preattached to the set, a biologically closed system, as medically defined, can be created.
The two stage system enables the collection of blood from a donor for separation into platelet-rich plasma and packed red cells. The red cell suspension is returned to the donor by means of the same needle used to withdraw the whole blood. The platelet-rich plasma is collected in a container. The machine and set are disconnected from the donor. The collected platelet-rich plasma is then separated into plasma and platelet concentrate, utilizing the second stage of the biologically closed set.
Another automated closed system for separating blood fractions is the CS-3000.RTM. cell separator sold by Baxter Healthcare Corporation. Still another system is the Model 50 separator sold by Haemonetics Corp. of Braintree, Mass.
During withdrawal of blood and its subsequent treatment/separation, anticoagulant must be added in order to prevent clotting of the blood within the disposable tubing and separation set during the separation or collection of the blood. The conventional method of administering anticoagulant during automated apheresis procedures is to add anticoagulant during the step of withdrawal of the whole blood from a donor's vein. Anticoagulant from an anticoagulant container is administered through tubing to a location just downstream from the phlebotomy needle at a tubing junction, where the anticoagulant tubing line merges with the unanticoagulated whole blood tubing line, adjacent the phlebotomy needle in the donor.
There are at least four separate reasons for the addition of anticoagulant to the donor's blood during an extracorporeal blood procedure. The first reason is to prevent the blood from clotting as it travels through the various tubes to the blood separator of the disposable set. The second reason is to prevent the blood from clotting as it is being separated. All separators require some exposure of blood to fluid shear stresses and these shear stresses can induce coagulation or agglomeration. The third reason is to prevent the separated cells from coagulation as they are being pumped through reinfusion filters and back to the donor. The fourth reason is to provide enough nutrients and sufficient pH buffering to permit storage of the separated blood component for the required duration of time.
The demand for anticoagulant in each of the four general steps identified above depends on the particular automated apheresis procedure. Some systems may induce significantly more shear stress during blood separation than other systems and therefore the upper limit demand for anticoagulant would be set by the separation step. Also, the separation technology used may have different stages wherein each separation stage may have its own, different demand level for the amount of anticoagulant in the blood. For example, if an intermediate stage separation such as platelet-rich plasma is collected first and then a secondary stage separation is utilized to separate the platelet-rich plasma (PRP) into plasma and platelet concentrate, there may be different requirements for anticoagulant at these two stages.
Alternatively, if the separated blood product is platelets for example and if the requirement is to store the platelets for five days, this relatively lengthy platelet storage period can often require more anticoagulant than any other stage in the blood withdrawal and separation procedure.
The addition of different amounts of anticoagulant to different blood components in manual (non-automated) blood collection is identified in "Platelet Concentrates from Acidified Plasma: A Method of Preparation Without the Use of Additives", Wanda S. Chappell. As best understood, the procedure explained therein utilized different aliquots of anticoagulant in different blood component containers to better optimize the amount of anticoagulant in a collected blood component.
Generally, the prior art has dealt with the issue of anticoagulant demand in automated procedures by adding to the whole blood, almost immediately upon its withdrawal from the donor, enough anticoagulant to meet the highest anticoagulant demand level during the entire withdrawal, separation, return and storage procedure. The anticoagulant is added adjacent the phlebotomy needle. The anticoagulant mixes with the whole blood upon being withdrawn from the donor. The prior art systems have been directed to adding as much anticoagulant as necessary to prevent clotting, with attention being paid to an upper limit dosage of anticoagulant, beyond which a so-called "citrate reaction" may occur in the donor upon return of an anticoagulated blood component to the donor. For example, with same blood separation systems, anticoagulant ratios of up to one part of anticoagulant to eight parts anticoagulated whole blood are used. In plasma collection procedures using the Autopheresis-C.RTM. device, typically six percent anticoagulant is used, but users have the ability to alter this percentage from four percent to eight percent. For platelet collection procedures with the Autopheresis-C.RTM. device, anticoagulant levels of six percent to eight percent are utilized. By the nature of some of these apheresis systems, it would be difficult to separate the four anticoagulant demand stages outlined above and have different amounts added depending on the individual stage.
For example, in the Haemonetics Model 50 Device, there are no intermediate stages in the separation process. If the goal is to make platelet concentrate, the platelet concentrate is derived directly from the whole blood, not from an intermediate component such as platelet-rich plasma for example. In other systems, such as the CS-3000.RTM. device there are intermediate stages. For example, if plateletpheresis is the objective, platelet-rich plasma is initially separated from whole blood. Then platelet-rich plasma is separated into platelet concentrate. In the CS-3000.RTM. device, this is done utilizing separate blood component containers within a closed system, within a centrifuge bowl. The Autopheresis-C.RTM. device, in conjunction with a disposable set, separates these components in completely separate stages, but in a single closed system. The platelet-rich plasma is harvested from the donor's blood and the donor is subsequently disconnected. In the next stage, the collected platelet-rich plasma is converted to platelet concentrate and platelet-poor plasma and these become two products of the procedure.
There has been, up until now, no automated blood component separation equipment and procedure for optimizing anticoagulant use during different steps of the automated apheresis procedure. Until now, there has been no recognition of the desirability of reducing the amount of anticoagulant added to whole blood before the separation step. There has been no automated procedure for optimizing the functional characteristics of different blood components in an automated procedure by adding aliquots of anticoagulant or other fluid at different stages in the apheresis procedure.